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Ann Oncol. 2017 Jun 1;28(6):1346-1351. doi: 10.1093/annonc/mdx124.

Pazopanib in advanced germ cell tumors after chemotherapy failure: results of the open-label, single-arm, phase 2 Pazotest trial.

Author information

1
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
2
Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
3
Department of Radiology, Interventional Radiology, Nuclear Medicine and Radiotherapy, National Cancer Institute, 20133 Milan, Italy.
4
Pharmacy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
5
Nuclear Medicine and PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
6
Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
7
Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale deiTumori, Milano, Italy.
8
Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.

Abstract

Background:

Therapeutic options for patients with chemoresistant germ cell tumors (GCTs) are limited. Pazopanib is a selective tyrosine kinase inhibitor with distinct antiangiogenic activity. We aimed to evaluate pazopanib activity in patients with refractory GCT.

Patients and methods:

In the open-label, single-arm, phase 2 Pazotest study (NCT01743482), patient eligibility included failure of ≥2 platinum-based regimens, and allowed prior high-dose chemotherapy administration. Patients were given pazopanib 800 mg/day until disease progression (PD) or onset of unacceptable toxicity. Measurements of serum tumor markers (STM), computed tomography and FDG-PET were carried out at baseline, after 4 weeks of pazopanib treatment, and every 8 weeks thereafter. PD was defined as increasing levels of STM, increasing size of non-teratomatous masses, or appearance of new lesions. The study primary endpoint was progression-free survival (PFS, H0: 3-month PFS ≤ 10%, H1: ≥25%, α = 5%, β = 20%).

Results:

Forty-three patients were enrolled from May 2013 to July 2016. The number of prior chemotherapy regimens was: 2 (11.6%), 3 (51.2%), >3 (37.2%). Grade 3 adverse events were observed in six patients (13.9%). Overall, 70.3% of patients had reduced levels of STM after 4 weeks. There were 2 partial responses (4.7%), 19 cases of stable disease, and 16 cases of PD (6 not evaluable by RECIST). The median follow-up duration was 29.6 months. The 3-month PFS probability was 12.8% [95% confidence interval (CI): 5.7%-28.9%]. The 24-month OS probability was 14.2% (95% CI: 6.0%-33.7%). In patients with a >50% decline in STM, the 24-month OS probability was 24.1% (95% CI: 8.3%-69.6%). The small sample size was the major limitation.

Conclusions:

Despite pazopanib showed potent but short-lived activity in refractory GCT, long-term survival was obtained in a proportion of treated patients. According to the kinetics of pazopanib activity, this drug may be investigated in less pre-treated patients as an optimal bridging therapy preceding and/or combined with salvage chemotherapy.

KEYWORDS:

germ cell tumors; pazopanib; salvage therapy; testicular cancer

PMID:
28383677
DOI:
10.1093/annonc/mdx124
[Indexed for MEDLINE]

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